The study of the androgen receptor (AR), both its assay in tissues of clinical significance such as prostate cancer and its purification for antibody production to permit further characterization, has lagged behind the study of other steroid receptors. This is due in part to the relatively low number of AR molecules in most target cells, and also to the receptor's relatively low stability. To help solve or circumvent these problems, I here propose to apply my experience in attaching side chains to several classes of steroid molecules without disrupting their receptor affinity, to the development of four new tools for the study of androgen receptor and andorgen action. (1) Sensitivity of the AR assay would be greatly enhanced by an 125I-labelled ligand. Two families of dihydrotestosterone (DHT) derivatives, 17 alpha-iodovinyl-DHT's and 17 alpha-iodoalkynyl- DHT's, will therefore be synthesized and their 125I forms tested for AR affinity and stability. (2) There is now evidence that steroid receptors might be detectable by flow cytometry, given stable, high affinity fluorescent conjugates. Several such conjugates derived from 17 alpha-iodoalkynyl-DHT's will therefore be synthesized and tested for their ability to identify AR-containing cells flow cytometrically. (3) Affinity chromatography is probably the optimum route for receptor purification. Now affinity beads based on these 17 alpha- iodoalkynyl-DHT's will thus be perpared, and compared for their ability to specifically bind AR from crude cytosols and to release the AR intact again on incubation with concentrated ligand. (4) Studies of androgen action in vivo depend on radioimmunoassay of circulating active androgens. The specificity of existing RIA antibodies, however, does not parallel androgen affinity for AR and biological activity. New antibodies will therefore be produced using as immunogen BSA-DHT conjugates derived from 17 alpha-iodoalkynyl-DHT's, since these immunogens will be expected to retain AR affinity, and many of the resulting antibodies should thus parallel the receptor in their steroid specificity. The development of these tools can be expected to accelerate our developing understanding of the biological distribution and role of the androgen receptor, and of its significance for prognosis and treatment of endocrine-dependent tumors.